Summary/Abstract Dentalimplantsarebecominganincreasinglypopularoptionvs.dentures,bridges,andotherdental prostheticsduetogreaterpatientsatisfactionandbetterlong-termoutcomes.However,osseointegrated dentalimplantsrequirestrong,healthyboneforimplantationtobesuccessful.Whilesuccessratesfor osseointegrateddentalimplantsarerelativelyhigh(~90%),adrasticincreaseinthenumberofimplantation proceduresisexpectedtooccurduetotheincreasingpopularityoftheprocedurewithpatientsandclinicians, aswellasdemographicfactorssuchasanincreasednumberofagingandelderlypatientsthatrequiredental prostheses.Faileddentalimplantationscanleadtoasignificantcostandcareburdentopatientsandtothe healthcaresystem,andinitialfailuresoftenmeanthatadditionalattemptsatimplantationinthesamesiteare notpossible.Together,thesefactorssignaltheneedforaclinicaltoolthatwillincreasetherateof osseointegrateddentalimplantsuccess,particularlyinpatientswhoareathigherriskforfailureduetothe inadequatepresenceofhigh-qualityboneinwhichtoplacetheimplant.NaturemiRI,LLChasdevelopeda novelmethodofmicroRNA(miR)inhibitionusingabiologicallynativemoleculecomposedofnucleicacidswith auniquesecondarystructure,allowingittobindanddegradeorsequestermaturemiRs.Theinhibitionof bindingmaturemiRstotheirmRNAtargetsaltersproteinproductioninthecell.Ithasbeenestablishedinour preliminarystudiesandpreviouslypublishedreportsthatmiR-200ainhibitsosteogenicdifferentiationand increasesthepro-inflammatoryresponse.OurPhaseIprojectgoalistodemonstratethatbyinhibitingmiR- 200ainvitroandinananimalmodel,wecanincreaseratesofosteogenesisandenhancethequalityof regrownbone.DuringPhaseI,wewillanalyzebonehardness,mineralcontent,anddensityduringosteogenic differentiationandinanartificialwound-healingmodel.Wealsointendtodemonstratethatthenucleicacid basedcompositionofourinhibitionmethodnegatestheriskofsystemictoxicity?aconcernthatexistswiththe useofsyntheticallymodifiedoligonucleotidemiRinhibitionmethods.PhaseIsuccesswillsetthestagefora largerPhaseIIdemonstrationprojectfocusedonlarger-scaletestingandvalidationoftheenvisionednewtool forthedentalclinic?ananti-miR-200a-infusedcollagenspongethatcouldbeusedintoothextraction proceduresinanticipationoffutureosseointegrateddentalimplantation.Successwillalsoestablish therapeuticproofofconceptforthisnewmiRinhibitionmethod,ultimatelyopeningthedoorforanimportant rangeofadditionaltherapeuticapplicationsinthedentalfieldandbeyond.NaturemiRI?sexperiencedteamof dentalresearchersisestablishedandwell-suitedtoaddressthescientificquestionsregardingtheproposed application.NaturemiRIleadershipalsoincludesasmallbutexperiencedbusinessdevelopmentteamthatis workingdiligentlyoncommercializationactivitiesregardingthemanypotentialapplicationsofthistechnology.